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High-dose Cephalexin for Cellulitis (HI-DOCC) (HI-DOCC)

Primary Purpose

Cellulitis

Status
Recruiting
Phase
Phase 4
Locations
Canada
Study Type
Interventional
Intervention
Cephalexin
Cephalexin
Sponsored by
Ottawa Hospital Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cellulitis focused on measuring Cellulitis, Cephalexin, Oral antibiotics, Treatment failure

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Adults (age ≥18 years) diagnosed with non-purulent cellulitis and determined by the treating emergency physician to be eligible for outpatient oral antibiotics. Exclusion Criteria: Age <18 years; Patient already taking oral antibiotics; Treating physician decides IV antibiotics are required; Abscess requiring an incision and drainage procedure; Known prior cellulitis secondary to methicillin-resistant Staphylococcus aureus (MRSA); Cellulitis secondary to a human or animal bite wound; Penetrating wound or water exposure resulting in cellulitis; Surgical site infection; Patient found at a follow up visit to have an alternative, non-infectious etiology (e.g., deep vein thrombosis); bilateral symptoms (e.g., both legs involved); Malignancy and currently being treated with chemotherapy; Solid organ or bone marrow transplant recipient; Renal impairment with an estimated glomerular filtration rate <30 mL/min documented on the health record at any time within the past three months; Allergy to cephalosporins or history of anaphylaxis to penicillin; Inability to provide informed consent

Sites / Locations

  • The Ottawa HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

High Dose Cephalexin

Standard Dose Cephalexin

Arm Description

The intervention is high-dose cephalexin (1000mg PO QID) for seven days

The comparator is standard-dose cephalexin (500mg PO QID) plus oral placebo for seven days

Outcomes

Primary Outcome Measures

Number of Participants with Oral Antibiotic Treatment Failure
defined as a change in antibiotic (change in class of oral antibiotic or step up to IV therapy) within 7 days due to worsening infection. Any of the following meet criteria for worsening infection (at day 3 or 8 follow-up): (1) New fever (temperature ≥38.0C) or persistent fever at follow-up; (2) Increasing area of erythema (in cm2) ≥20% from baseline; or (3) Increasing pain ≥2 points from baseline (using the numeric rating scale).

Secondary Outcome Measures

Number of Participants with clinical cure
defined as absence of pain, erythema, and fever
Number of Participants with clinical response
defined as a reduction in lesion size ≥20% compared to baseline
Number of Participants with unplanned visits to a healthcare provider for cellulitis
Number of Participants with unplanned hospitalization for cellulitis
Number of Participants with adverse events
classified as serious or other and will be assessed at day 30 follow up. Serious adverse events will include anaphylaxis to study medication, development of Clostridium difficile colitis or unexpected deaths related to the infection or treatment. Other adverse events include nausea, vomiting, diarrhea, abdominal pain and rash.
Number of Participants with antibiotic intolerance
defined as change in treatment due to adverse events
Number of Participants with antibiotic allergy
defined as change in treatment due to skin, respiratory, cardiovascular, or gastrointestinal symptoms requiring treatment with an antihistamine and/or epinephrine.
Number of Participants with medication adherence
with full adherence defined as patients who report taking all study medication over 7 days
Number of Participants with health-related quality of life
Measured using EuroQol-5D-5L instrument at index visit and all follow-ups (days 3,8 and 30)

Full Information

First Posted
May 1, 2023
Last Updated
September 20, 2023
Sponsor
Ottawa Hospital Research Institute
Collaborators
Network of Canadian Emergency Researchers (NCER), The Ottawa Hospital Academic Medical Association
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1. Study Identification

Unique Protocol Identification Number
NCT05852262
Brief Title
High-dose Cephalexin for Cellulitis (HI-DOCC)
Acronym
HI-DOCC
Official Title
High-dose Cephalexin for Cellulitis (HI-DOCC)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 30, 2023 (Actual)
Primary Completion Date
August 31, 2025 (Anticipated)
Study Completion Date
August 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ottawa Hospital Research Institute
Collaborators
Network of Canadian Emergency Researchers (NCER), The Ottawa Hospital Academic Medical Association

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Cellulitis is a common condition diagnosed and managed in the ED that carries significant burden on healthcare systems globally. Cellulitis is the 8th most common reason patients present to an ED in Canada. Among middle-aged patients (45-64 years) it is the 5th most common reason to visit an ED. This disease is responsible for significant healthcare system burden due to high hospitalization rates and subsequent costs. The Investigators conducted a health records review at two large urban EDs in Ottawa, and found that 29.6% of patients with cellulitis are admitted to hospital. In a separate study, The investigators found that the mean cost of care to hospitalize cellulitis patients for IV antibiotics was $10,145 CDN.
Detailed Description
Background Non-purulent cellulitis is a bacterial skin and soft tissue infection of the subcutaneous tissue. Group A streptococcus (Streptococcus pyogenes), beta-hemolytic streptococci and methicillin-susceptible Staphylococcus aureus are the most common bacteria causing non-purulent cellulitis. Patients typically present to the emergency department (ED) with pain, redness, swelling and induration (skin hardening due to inflammation) of the affected skin. A minority of patients may have fever or tachycardia. The diagnosis of cellulitis is clinical. Once the diagnosis is made, antibiotic treatment is initiated. The emergency physician must select the appropriate agent, oral versus intravenous (IV) route, dose, frequency and duration. Rationale For ED adult patients with cellulitis, how does high-dose (1000 mg QID) cephalexin compare with standard-dose (500 mg QID) cephalexin with respect to antibiotic treatment failure, adverse events and health service utilization (i.e., need for IV antibiotics, unscheduled return ED visits and hospitalization)? Hypotheses (superiority): Treatment with high-dose cephalexin will lead to lower rates of oral antibiotic treatment failure than using standard-dose cephalexin. Methods: Study Design & Setting The investigators will conduct a multicentre, parallel-arm double-blind, individually randomized trial comparing high-dose (1000 mg) cephalexin to standard-dose (500 mg) cephalexin to treat ED adult patients with cellulitis. This is a superiority trial. The trial will be conducted at 8 Canadian EDs. A total sample size of 446 patients (223 per group) will be required. Study Population Inclusion Criteria The Investigators will include adults (age ≥18 years) diagnosed with non-purulent cellulitis and determined by the treating emergency physician to be eligible for outpatient oral antibiotics. Trial Intervention The study interventions are two accepted doses of oral cephalexin. The interventions will begin following randomization. High-dose cephalexin. Patients randomized to this arm will receive a seven-day medication package of cephalexin 1000 mg (two 500 mg tablets per dose) to be taken four times daily. A duration of seven days was selected as this was the most common prescription duration in a survey of Canadian emergency physicians.32 The antibiotic pills will be provided in a dosette organized by dose and day. Standard-dose cephalexin. Patients randomized to this arm will receive a seven-day medication package of cephalexin 500 mg (one 500 mg tablet and one placebo tablet per dose) to be taken four times daily. Blinding. Both cephalexin and placebo will be encased in identical capsules, prepared and packaged independently by an external pharmacy. The patients, treating physician and research team (including outcome adjudicators) will be blinded. Primary Outcome: Oral Antibiotic Treatment Failure The primary outcome is outpatient oral antibiotic treatment failure, defined as a change in antibiotic (change in class of oral antibiotic or step up to IV therapy) within 7 days due to worsening infection. Secondary Outcomes Clinical cure, defined as absence of treatment failure criteria, evaluated at day 8 and 30 Clinical response, defined as a reduction in lesion size ≥20% compared to baseline, evaluated at the day 3 and day 8 follow-up assessments Unplanned visits to a healthcare provider (ED, family doctor) within 30 days Unplanned hospitalization within 30 days. Adverse events will be classified as serious or other and will be assessed at day 30 follow up. Serious adverse events will include anaphylaxis to study medication, development of Clostridium difficile colitis or unexpected deaths related to the infection or treatment. Other adverse events include nausea, vomiting, diarrhea, abdominal pain and rash. Antibiotic intolerance, defined as change in treatment due to adverse events. Antibiotic allergy, defined as change in treatment due to skin, respiratory, cardiovascular, or gastrointestinal symptoms requiring treatment with an antihistamine and/or epinephrine. Medication adherence, with full adherence defined as patients who report taking all study medication over 7 days Health-related quality of life measured using the EuroQoL-5D-5L36 instrument IMPORTANCE Cellulitis is a common cause of ED visits, and many patients are hospitalized. Current evidence is lacking regarding the optimal management of cellulitis. If high-dose cephalexin is found to be superior to standard-dose cephalexin, this will change practice, with the potential to reduce unnecessary IV antibiotic use, hospitalization, and costs. The results will help inform future skin and soft tissue infection treatment guidelines.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cellulitis
Keywords
Cellulitis, Cephalexin, Oral antibiotics, Treatment failure

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
The Investigators will conduct a parallel arm double-blind randomized controlled trial.
Masking
ParticipantCare ProviderInvestigator
Masking Description
Eligible patients will be randomized (1:1) to high-dose versus standard-dose arms. The randomization sequence will be computer-generated by a statistician
Allocation
Randomized
Enrollment
446 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
High Dose Cephalexin
Arm Type
Experimental
Arm Description
The intervention is high-dose cephalexin (1000mg PO QID) for seven days
Arm Title
Standard Dose Cephalexin
Arm Type
Active Comparator
Arm Description
The comparator is standard-dose cephalexin (500mg PO QID) plus oral placebo for seven days
Intervention Type
Drug
Intervention Name(s)
Cephalexin
Other Intervention Name(s)
High-dose cephalexin
Intervention Description
1000 mg PO QID for 7 days
Intervention Type
Drug
Intervention Name(s)
Cephalexin
Other Intervention Name(s)
Standard-dose cephalexin
Intervention Description
500 mg PO QID plus oral placebo for 7 days
Primary Outcome Measure Information:
Title
Number of Participants with Oral Antibiotic Treatment Failure
Description
defined as a change in antibiotic (change in class of oral antibiotic or step up to IV therapy) within 7 days due to worsening infection. Any of the following meet criteria for worsening infection (at day 3 or 8 follow-up): (1) New fever (temperature ≥38.0C) or persistent fever at follow-up; (2) Increasing area of erythema (in cm2) ≥20% from baseline; or (3) Increasing pain ≥2 points from baseline (using the numeric rating scale).
Time Frame
7 days
Secondary Outcome Measure Information:
Title
Number of Participants with clinical cure
Description
defined as absence of pain, erythema, and fever
Time Frame
evaluated at day 8 and day 30
Title
Number of Participants with clinical response
Description
defined as a reduction in lesion size ≥20% compared to baseline
Time Frame
evaluated at days 3 and 8
Title
Number of Participants with unplanned visits to a healthcare provider for cellulitis
Time Frame
30 days
Title
Number of Participants with unplanned hospitalization for cellulitis
Time Frame
30 days
Title
Number of Participants with adverse events
Description
classified as serious or other and will be assessed at day 30 follow up. Serious adverse events will include anaphylaxis to study medication, development of Clostridium difficile colitis or unexpected deaths related to the infection or treatment. Other adverse events include nausea, vomiting, diarrhea, abdominal pain and rash.
Time Frame
30 days
Title
Number of Participants with antibiotic intolerance
Description
defined as change in treatment due to adverse events
Time Frame
7 days
Title
Number of Participants with antibiotic allergy
Description
defined as change in treatment due to skin, respiratory, cardiovascular, or gastrointestinal symptoms requiring treatment with an antihistamine and/or epinephrine.
Time Frame
7 days
Title
Number of Participants with medication adherence
Description
with full adherence defined as patients who report taking all study medication over 7 days
Time Frame
7 days
Title
Number of Participants with health-related quality of life
Description
Measured using EuroQol-5D-5L instrument at index visit and all follow-ups (days 3,8 and 30)
Time Frame
30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Adults (age ≥18 years) diagnosed with non-purulent cellulitis and determined by the treating emergency physician to be eligible for outpatient oral antibiotics. Exclusion Criteria: Age <18 years; Patient already taking oral antibiotics; Treating physician decides IV antibiotics are required; Abscess requiring an incision and drainage procedure; Known prior cellulitis secondary to methicillin-resistant Staphylococcus aureus (MRSA); Cellulitis secondary to a human or animal bite wound; Penetrating wound or water exposure resulting in cellulitis; Surgical site infection; Patient found at a follow up visit to have an alternative, non-infectious etiology (e.g., deep vein thrombosis); bilateral symptoms (e.g., both legs involved); Malignancy and currently being treated with chemotherapy; Solid organ or bone marrow transplant recipient; Renal impairment with an estimated glomerular filtration rate <30 mL/min documented on the health record at any time within the past three months; Allergy to cephalosporins or history of anaphylaxis to penicillin; Inability to provide informed consent
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Krishan Yadav, MD
Phone
613-798-5555
Ext
19489
Email
kyadav@toh.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Gabriel Sandino-Gold
Phone
613-798-5555
Email
gsandino@ohri.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Krishan Yadav, MD
Organizational Affiliation
Ottawa Hospital Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Ottawa Hospital
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1Y 4E9
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Krishan Yadav
Phone
613-798-5555
Email
kyadav@toh.ca
First Name & Middle Initial & Last Name & Degree
Gabriel Sandino-Gold
Email
gsandino@ohri.ca

12. IPD Sharing Statement

Plan to Share IPD
No

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High-dose Cephalexin for Cellulitis (HI-DOCC)

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